Background: Clinical manifestations of the syphilis can occur in the mouth and in the perioral region. This study aimed to investigate the knowledge about syphilis and its oral manifestations among dental students and to discuss the role of the dentist in prevention and control of this disease. Methods: This is a cross-sectional study carried out with 171 dentistry students enrolled in the second, third, fourth and fifth years in the first semester of 2019 from the Federal University of Espírito Santo, Brazil. Data collection was performed by a questionnaire containing 16 questions answered by students in classroom. Analyses of absolute and relative frequency were performed. To perform association among variables, the Chi-square test (or Fisher's exact test with Yates correction) was performed with 5% significance level. Results: Overall, 169 students participated in the study. Only 40 (46.4%) students correctly answered the question about disease stages. Almost all participants answered that syphilis has oral manifestations; however, only 44 (25.7%) answered the question correctly. Regarding differential diagnoses of other oral lesions, only 63 (37.3%) reported knowledge on this subject. There was a statistically significant association between student’s educational level and knowledge about the etiological agent (p<0.0001), clinical manifestations (p<0.0001), disease stages (p<0.0001), oral manifestations (p<0.0001) and drugs (p = 0.005) related to the disease. Conclusions: Participants showed important gaps in their knowledge about syphilis and its oral manifestations. Our findings, together with the increased number of new cases of the disease in the world, reinforce the need for training dental professionals with knowledge about early diagnosis, effective treatment and follow-up of syphilis cases.